This article describes the discovery of novel potent muscarinic receptor antagonists identified during a search for more active histamine H₃ receptor (H₃R) ligands. The idea was to replace the flexible seven methylene linker with a semirigid 1,4-cyclohexylene or p-phenylene substituted group of the previously described histamine H₃R antagonists ADS1017 and ADS1020. These simple structural modifications of the histamine H₃R antagonist led to the emergence of additional pharmacological effects, some of which unexpectedly showed strong antagonist potency at muscarinic receptors. This paper reports the routes of synthesis and pharmacological characterization of guanidine derivatives, a novel chemotype of muscarinic receptor antagonists binding to the human muscarinic M₂ and M₄ receptors (hM₂R and hM₄R, respectively) in nanomolar concentration ranges. The affinities of the newly synthesized ADS10227 (1-{4-{4-{[4-(phenoxymethyl)cyclohexyl]methyl}piperazin-1-yl}but-1-yl}-1-(benzyl)guanidine) at hM₂R and hM₄R were 2.8 nM and 5.1 nM, respectively.

Investigating novel, biologically-active coordination compounds that may be useful in the design of breast anticancer, antifungal, and antimicrobial agents is still the main challenge for chemists. In order to get closer to solving this problem, three new copper coordination compounds containing thiazole-based derivatives were synthesized. The structures of the synthesized compounds and their physicochemical characterization were evaluated based on elemental analysis, ¹H and ^l3C nuclear magnetic resonance (NMR), flame atomic absorption spectroscopy (F-AAS), single-crystal X-ray diffraction, thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FTIR). The pharmacokinetics were studied using SwissADME. The results obtained from the computational studies supported the results obtained from the MTT analysis, and the antimicrobial activity was expressed as the minimum inhibitory concentration (MIC).

Bryostatin 1, a natural macrolide isolated from Bugula neritina, is a potent modulator of protein kinase C (PKC) isoforms with promising anticancer properties. In numerous in vitro studies, bryostatin 1 has been shown to inhibit tumor cell proliferation and induce differentiation and apoptotic cell death in a wide range of cell lines, including leukemia, lymphoma, glioma, and solid tumors such as ovarian and breast cancer. Its antitumor activity, both as monotherapy and in combination with conventional chemotherapy, has been confirmed in in vivo models, where synergistic effects have been observed, including sensitization of tumor cells to cytostatic agents. Despite promising preclinical findings, phase I and II clinical trials have not yielded the expected results, suggesting limited efficacy of the macrolide as a single agent with a relatively favorable safety profile. Current research directions focus on optimizing dosing regimens, combining bryostatin 1 with other anticancer drugs and identifying predictive biomarkers of response. This article reviews the current state of knowledge on the anticancer effects of bryostatin 1, analyzing available data from in vitro, in vivo, and clinical trials and discussing potential directions for further translational research.

This study examines the properties of novel guanidines, designed and synthesized as histamine H₃R antagonists/inverse agonists with additional pharmacological targets. We evaluated their potential against two targets viz., inhibition of MDA-MB-231, and MCF-7 breast cancer cells viability and inhibition of AChE/BuChE. ADS10310 showed micromolar cytotoxicity against breast cancer cells, combined with nanomolar affinity at hH₃R, and may represent a promising target for the development of an alternative method of cancer therapy. Some of the newly synthesized compounds showed moderate inhibition of BuChE in the single-digit micromolar concentration ranges. H₃R antagonist with additional AChE/BuChE inhibitory effect might improve cognitive functions in Alzheimer’s disease. For ADS10310, several in vitro ADME-Tox parameters were evaluated and indicated that it is a metabolically stable compound with weak hepatotoxic activity and can be accepted for further studies.